Preparation of Multifunctional Liposomes as a Stable Vaccine Delivery-Adjuvant System by Procedure of Emulsification-Lyo

Liposomes have been proven to be useful carriers for vaccine antigens and can be modified as a versatile vaccine adjuvant-delivery system (VADS). To fulfill efficiently both functions of adjuvant and delivery, the liposomes are often modified with differe

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Introduction Vaccination is the most cost-effective and best prophylactic strategy against many diseases [1]. The conventional vaccines are usually live attenuated or inactivated pathogenic organisms which, after administration, can induce robust immunity in the vaccinated subjects against the related microbes. However, live attenuated pathogens might mutate to be pathogenic and even lead to more severe outcomes; while the inactivated microorganisms may stimulate much weaker and even target-deviated immune response. To overcome the drawbacks associated with conventional vaccines based on whole pathogens, recently subunit vaccines which contain only the essential antigens and, therefore, have defined components are developed, with the anticipation that the potential risks confronted by the conventional vaccines may be reduced [2, 3]. However, due to lack of other microbial components which may not only protect the antigen but also be a pathogen-associated molecular pattern (PAMP) for mammalian immune systems, subunit vaccines are rather unstable and often induce weak immune responses against pathogens. To overcome the weaknesses of subunit vaccines [4], a vaccine carrier with composition mimicking the components of pathogenic organisms has been developed as the vaccine adjuvant-delivery system (VADS) to protect antigens from the environmental damages and even deliver them to specific lymphocytes to initiate effective immune responses [4–6]. Currently, numerous particulate carriers, such as emulsions, liposomes, PLGA particles, silico nanocarriers, and, notably, VLPs (virus-like particles), have been developed as a VADS. In addition, to be recognized and thus taken up by APCs (antigen-presenting

Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_41, © Springer Science+Business Media New York 2016

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Ning Wang and Ting Wang

cells), the vaccine carriers are often decorated with PAMP molecules and/or the molecules as ligands to the receptors expressed on the immune cell surfaces, featuring a multifunctional targeting VADS [2, 7–10]. Among various carriers, liposomes have attracted much research interests due to their intrinsic adjuvant properties and the easiness for achieving diverse surface decorations, representing a powerful VADS with some additional advantages of safety, biocompatibility, and wide agent-loading range [11]. Also, various VADS based on multifunctional liposomes have been developed utilizing the specific binding affinities between functional molecules on the carrier and special features expressed or engendered by the aims. For example, recently, we successfully prepared a multifunctional liposome that was dually anchored with a TLR4 ligand lipid A and a synthetic molecule having a distal mannose group and termed mannosylated/lipid A-liposomes (multifunctional liposomes). This kind of multifunctional liposomes proved highly effective in both targeting delivery of vacc